Why is there no HIV vaccine?

In case it’s somehow escaped your notice, we are living in a pandemic, and we’ve gone from not knowing about COVID-19, to having a vaccine in under a year. But we’ve been less lucky with HIV: decades later, there is still no vaccine. Why? Anna Maria Geretti is from the University of Liverpool, and spoke to Chris Smith about the struggles of a HIV vaccine...

Anna Maria - Yes, indeed. I think that we have been disappointed. I believe the first vaccine study was done in 1986 and it's been quite a long time and perhaps there have been 250 studies that have given us disappointing results. So is it possible? We continue to believe it is. Is it needed? I think we should perhaps remember that in 2019 alone there were about 1.7 million new infections in the world. And if we really want to be successful in limiting the number of new infections, we need to develop an effective vaccine. Is it biologically plausible? Is it possible to achieve a vaccine? Well certainly through these three decades and more of studies, we have learned a lot about HIV, the biology, how the body responds to the infection and yes, we've had setbacks, but we've also had some breakthroughs. I think that we mentioned, for example, how difficult it is to control the virus because the virus continues to change and escapes body responses, the immune responses. There are also other mechanisms that the virus uses to evade the control, and a major breakthrough I would say has been been the understanding of the fact that the virus uses sort of decoys - it triggers the immune system in chasing after the wrong type of parts of the virus, protecting away the true vulnerable part of the virus. And this has been a recent, relatively recent understanding that gives us hope that we may be able to really direct immune responses towards the right part of the virus, the right antigen, the right component of the virus, and that is the vulnerable parts of the virus. So we discovered these responses as being broadly effective against, against the virus.

Chris - Are there sort of any bits of evidence you can point to that would reassure us that it is possible to make an immune response against the business end of the virus so that even despite its best efforts to decoy our immune system in the way you've just been describing, we can nail it nonetheless?

Anna Maria - Well, I think it's important to remember that we have some individuals that are exposed to HIV, but not infected. And we've also gained a lot of understanding about the interaction between the virus and immune system from studying people that are called elite controllers. These are people that are infected with HIV so they have evidence of the infection. However, they do not show progression of the disease. Somehow they found a way of keeping the virus at bay, keeping the virus under control, and that is without the need for HIV treatment, without the need for antiviral.

Chris - And how common is that? How many of those people are there?

Anna Maria - There aren't that many, there are a handful in each centre and indeed it's not a common occurrence, but we have learned a lot from studying this patient population. And also, as I said, we also learned that some people can make really very effective antibody body responses - what we call broadly neutralizing antibody responses. So responses that actually are directed against the vulnerable parts of the virus.

Chris - So I suppose your strategy would be, well let's study these people that, rare as they are, do appear to have an ability to control the virus. And then if we can work out what has happened in them, we can make the same thing happen in people who otherwise wouldn't be so fortunate. So we've basically got to build some kind of vaccine capable of making the normal person's immune response behave like one of these so-called elite controllers that you were just talking about.

Anna Maria - Indeed, that is one strategy. And it's also effective to think about new ways of presenting the proteins of the virus, the antigen of the virus, to the immune system. New ways that may induce a response which is even better than what can be generated spontaneously in people that perhaps are elite controllers, so spontaneously managed to control the infection. It is plausible, scientifically plausible, that we may find a way of presenting the virus protein in a way that is better than what happens during natural infection. And I suppose that that's really, what we would love to be able to achieve in HIV.

Chris - It's strange though, isn't it, that we have managed to put so much effort over so many years into this and it has sidestepped us at every turn.

Anna Maria - Yes, it's been disappointing. However, I will say there have been some obstacles. There have also been cases when perhaps the scientific world was distracted, or perhaps was focusing on the wrong aspects of the virus, trying to induce the wrong type of immune responses, or perhaps pursuing ways of developing the vaccine that were not the most successful. We've had a number of setbacks that were significant, but I will say that we also have now a new opportunity. I would like to think that the COVID 19 pandemic and the success of the development of the vaccine, particularly with this new technology, for example of the RNA-based vaccines, I think it will generate a renewed enthusiasm for the development of HIV vaccine. Because it really shows how if you combine efforts, you know, academic efforts, efforts from pharma, interaction with regulators, so this combined focus and investment into trying to develop a COVID-19 vaccine has paid off and the use of new platforms has paid off. Has indeed shown that it's possible to induce responses which are better than natural infection.